The proposed research investigations are designed to determine how conditions affecting brain metabolism can alter CNS function with age. Included are studies to evaluate factors responsible for changes in energy dependent metabolic pathways the impairment of which by oxygen insufficiency can lead to cerebral functional abnormalities. This research involves a combined biochemical and biophysical approach, the latter being the application and development of nondestructive and nontraumatic optical methods, i.e. reflectance and transillumination spectrophotometry and microfluorometry, to continuously and simultaneously observe changes in functional and metabolic activities in the intact brain of young and aged animals. These techniques allow direct monitoring of changes in reduction/oxidation (redox) ratios of intramitochondrial respiratory chain intermediates, e.g., NAD/NADH and cytochromes, together with alterations in hemoglobin saturation levels and regional blood volume. We have proven such methods to be reliable for the detection of unsuspected pathological lesions and abnormalities in cerebral metabolism and vascular reactivity in the brains of aged animals under stress mediated conditions of high energy demand. The research design includes testing drugs reported to have beneficial effects on CNS metabolism with age and pharmacological agents known to effect cerebrovascular reactivity. Models of surgically induced stroke, e.g., middle cerebral artery occlusion, and hypotensive shock will be constructed. These procedures have been specifically designed to allow for an expendient assessment of pharmacological management possibilities in CNS functional recoverability with age.